Cd-exposed Group Research Articles

Bound phenolics extracts of jujube peel relieve cadmium-induced toxicity by reducing lipid accumulation of Caenorhabditis elegans.

To investigate the effect of bound phenolics extracts (BPEs) of jujube peel on relieving cadmium (Cd)-induced toxicity and its mechanism, the behavioral deficits, lipid accumulation, and fatty acid synthesis-related gene expression in Caenorhabditis elegans in Cd exposure group and BPEs improvement groups were determined and compared. The results showed that BPEs significantly improved Cd-induced behavioral deficits in C. elegans, and no significant differences could be found in low-dose (12.5µg/mL) and high-dose (100µg/mL) BPEs improvement groups. The treatment of BPEs effectively improved intestinal injury and lipofuscin and lipid accumulation. Especially, oil red O staining intensity in C. elegans treated with BPEs at 50µg/mL was reduced by 12.60%. BPEs significantly controlled the increase in content of C16:0, C16:1, C18:0, C18:1, and C18:2 induced by Cd by regulating the lipid accumulation in Escherichia coli OP50. Cd exposure induced lipid accumulation in C. elegans by upregulating oleic acid synthesis-related gene expression in E. coli OP50. Furthermore, BPEs treatment significantly downregulated the fatty acid synthesis-related gene expression in C. elegans and E. coli OP50. This research could reveal the mechanism of BPEs of jujube peel in relieving Cd-induced toxicity and provide a theoretical basis for the development of functional foods rich in polyphenols. PRACTICAL APPLICATION: Jujube peel, a by-product of jujube processing, is usually discarded due to its coarse texture. However, jujube peel has been proven to possess abundant polyphenols, polysaccharides, and cyclic adenosine phosphate. In addition, in our previous research, bound phenolics extracts (BPEs) of jujube peel were found to perform better in lowering lipid accumulation than that of free phenolics extracts. This study further investigate the effect of BPEs of jujube peel on relieving Cd-induced toxicity and its mechanism on the base of our previous research. It could realize the comprehensive utilization of by-products of jujube processing.

Developmental toxicity in zebrafish embryos exposed to single, binary, and tertiary mixtures of Cd, Pb, and As

The present study was carried out to investigate developmental toxicity to zebrafish upon exposure singly to cadmium chloride monohydrate (25 µg/L), or lead acetate (40 µg/L), or arsenic trioxide (40 µg/L), and their toxicological interactions upon exposure to combinations of Cd + Pb, Pb + As, Cd + As, and Cd + Pb + As for 120 h post fertilization. Cumulative mortality at 72, 96, and 120 h were significantly higher in all toxicity groups. Cd, Pb, and Pb + As exposure caused 92–100% mortality at 96 h of the exposure. The highest reduction of hatching rate was observed in the Pb + As group followed by the Cd + Pb group. The heart rate was significantly decreased in Cd, As, Cd + Pb, and Cd + Pb + As groups as compared to the control group. Body length, eye size, and cranium size were significantly affected in most of the toxicity groups. The exposure of Cd and Pb increased yolk sac size in the larvae as compared to other treatments. The Pb and Cd exposure group exhibited more tail and spinal deformities. The Cd + Pb exposure group exhibited pericardial and yolk sac edema in the larvae. There may be a possibility of toxicological interaction among Cd, Pb, and As, and may cause developmental defects in fish at the early life stages.

Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects.

The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague-Dawley (SD) rats were exposed to CdCl2 (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (p < 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (p < 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.

Sublethal Concentrations of Cadmium and Lead: Effects on Hemato-Biochemical Parameters and Tissue Accumulation in Wallagu attu.

The exposure of fish to heavy metals can significantly impact physiological processes and potentially lead to adverse health effects. This study assesses the effects of exposure to Cd and Pb sublethal concentrations in water on Wallagu attu. A total of 48 fish with an average body weight of 145.5 ± 26g were distributed among three groups (control, Cd-treated, and Pb-treated) within 60L fiberglass tanks. They were exposed to30% sublethal concentrations of Cd and Pb for durations of 1, 15, and 30 days. Following this exposure, an assessment was conducted on metal bioaccumulation and hemato-biochemical responses. Results revealed a significantly (P < 0.05) higher concentration of heavy metals in the fish tissues of metals exposed groups than in the control. The concentration of Cd and Pb increases in fish tissues (kidney > gills > intestine) with exposure time. In most cases, the Pb-exposed group exhibited significantly (P < 0.05) higher concentrations of Pb in different tissues than the Cd-treated group. With extended exposure time, the activities of CAT and SOD show a significant decrease in both Cd and Pb-treated groups. However, the reduction in activities was more pronounced in the Cd-exposed group. On 15 and 30 days, the levels of red blood cells (RBC), hemoglobin (HB), hematocrit (HCT), and total protein (TP) decrease in groups exposed to Cd and Pb. The cortisol and glucose levels exhibit a more noticeable (P < 0.05) increase with prolonged exposure to Cd and Pb than the control group. On day 30, the survival rate decreased more in the Pb-exposed group. The findings of this study indicate that exposure to sublethal doses of Cd and Pb induces stress in Wallagu attu, resulting in rapid changes in specific hemato-biochemical parameters.

Molecular mechanisms and physiological responses of rice leaves co-exposed to submicron-plastics and cadmium: Implication for food quality and security

The effects of co-exposure to aged submicron particles (aSMPs) and Cd as model contaminants on rice leaves via the foliar route were investigated. Thirty-day-old rice seedlings grown in soil were exposed to Cd (nitrate) through foliar spraying at concentrations of 1, 10, 50, 100, and 500 μM, with or without aSMP at a rate of 30 μg d−1. It was observed that Cd translocated from leaves to roots via stems even without co-exposure to SMP. Co-exposure can reduce cadmium levels in leaves. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analysis confirmed a significant reduction (29.3 − 77.9%) in Cadmium accumulation in the leaves of rice plants during co-exposure. Exposure to Cd resulted in physiological, transcriptomic, and metabolomic changes in rice leaves, disrupting 28 metabolism pathways, and impacting crop yield and quality. Exposure to both Cd and aSMPs can interfere with the Cd distribution in plants. Rice leaves exposed solely to Cd exhibit higher toxicity and Cd accumulation, compared to those co-exposed to Cd and aSMPs. The accumulation of Cd in plant leaves is enhanced with aSMPs, which may lead to more pronounced gene expression regulation and changes in metabolic pathways, compared to Cd exposure. Our study found that the independent Cd exposure group had higher Cd accumulation and toxicity in rice leaves compared to the combined exposure of Cd and aSMPs. We hypothesize that aged negatively charged SMPs can capture Cd and reduce its exposure in the free state while jointly inhibiting Cd-induced oxidative and chloroplast damage, thereby reducing the potential risk of Cd exposure in rice plants.

Paternal cadmium exposure induces glucolipid metabolic reprogramming in offspring mice via PPAR signaling pathway

In industrialized societies, the prevalence of metabolic diseases has substantially increased over the past few decades, yet the underlying causes remain unclear. Cadmium (Cd) is a hazardous heavy metal and pervasive environmental endocrine disruptor. Here, we investigate the effects of paternal Cd exposure on offspring glucolipid metabolism. Paternal Cd exposure (1 mg kg−1 body weight) impaired glucose tolerance, increased random serum glucose and fasting serum insulin, elevated serum total cholesterol, and low-density lipoprotein in offspring mice. Untargeted metabolomics analysis of male offspring liver tissue revealed that paternal Cd exposure can affect offspring glucolipid metabolic reprogramming, which involved biosynthesis of phenylalanine, tyrosine and tryptophan, biosynthesis of unsaturated fatty acids, metabolism of linoleic acid, arachidonic acid and α-linolenic acid. Transcriptome sequencing of male offspring liver tissue showed that arachidonic acid metabolism, AMPK signaling pathway, PPAR signaling pathway and adipocytokine signaling pathway were significantly inhibited in the Cd-exposed group. The mRNA expression levels of PPAR signaling pathway related genes (Acsl1, Cyp4a14, Cyp4a10, Cd36, Ppard and Pck1) were significantly decreased. The protein expression levels of ACSL1, CD36, PPARD and PCK1 were also significantly reduced. Collectively, our findings suggest that paternal Cd exposure affect offspring glucolipid metabolic reprogramming via PPAR signaling pathway.

Paternal cadmium exposure affects estradiol synthesis by impairing intracellular cholesterol homeostasis and mitochondrial function in offspring female mice

Cadmium (Cd) is a toxic heavy metal commonly found in nature and an endocrine disrupting chemical (EDC). Previous studies found that Cd can damage several organs, including the kidneys, bones, cardiovascular system and reproductive system. However, the effect of paternal Cd exposure on the offspring is unclear. In this study, 1 mg/kg of cadmium chloride (CdCl2) was injected intraperitoneally every other day in 8-week-old C57BL/6 J male mice to study the effects on their female offspring. Our results showed an increase in body weight, water intake and food intake in F1 female mice from the Cd-exposed group. The development of secondary follicles and antral follicles in the ovaries of Cd-treated was inhibited. Serum estradiol (E2) was found to be decreased. Further analysis revealed significant downregulation of StAR, P450scc, 17β-HSD, CYP17A1 and CYP19A1, which are related to E2 synthesis. Serum total cholesterol was increased and free cholesterol was reduced. Total cholesterol in ovarian tissue was decreased. qRT-PCR and Western blot analysis revealed a decrease in the mRNA and protein expression of HMGCR, LDLR, and ABCA1, which are associated with cholesterol homeostasis. Oil red O staining indicated that lipid droplets (LDs) were accumulated in ovarian tissues, while the expression of ATGL and HSL proteins associated with lipid droplet degradation was significantly downregulated. In juvenile female mice, ultrastructural alterations of mitochondria in the ovaries were observed by transmission electron microscopy (TEM). In adult female mice, the expression of proteins associated with mitochondrial dynamics (DRP1 and MFN2) was significantly reduced in the ovaries. Overall, our study suggests that paternal Cd exposure inhibits follicular development, and affects serum E2 synthesis by impairing cholesterol homeostasis and affecting mitochondrial function.

Cadmium influence on lipid metabolism in Sprague-Dawley rats through linoleic acid and glycerophospholipid metabolism pathways.

Cadmium (Cd) is widely distributed in the environment and easy adsorbed by living organisms with adverse effects. Exposure to Cd-contaminated food may disrupt lipid metabolism and increase human health risk. To study the perturbation effect of Cd on lipid metabolism in vivo, 24 male Sprague-Dawley (SD) rats were randomly assigned four groups and treated by Cd chloride solution (0, 1.375 mg/kg, 5.5 mg/kg, 22 mg/kg) for 14 days. The characteristic indexes of serum lipid metabolism were analyzed. Afterwards, untargeted metabolomics analysis was applied to explore the adverse effects of Cd on rats by liquid chromatography coupled with mass spectrometry (LC-MS). The results revealed that Cd exposure obviously decreased the average serum of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and caused an imbalance of endogenous compounds in the 22 mg/kg Cd-exposed group. Compared with the control group, 30 metabolites with significant differences were identified in the serum. Our results indicated that Cd caused lipid metabolic disorders in rats by disrupting linoleic acid and glycerophospholipid metabolism pathways. Furthermore, there were three kinds of remarkable differential metabolites-9Z,12Z-octadecadienoic acid, PC(20:4(8Z,11Z,14Z,17Z)/0:0), and PC(15:0/18:2(9Z,12Z)), which enriched the two significant metabolism pathways and could be the potential biomarkers.

Protective Effect of Astragaloside IV against Cadmium-Induced Damage on Mouse Renal Podocytes (MPC5).

In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 μM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 μM) was significantly reduced, while the death rate in the medium dose group (25 μM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.

Insight into the effect of a heavy metal mixture on neurological damage in rats through combined serum metabolomic and brain proteomic analyses

The heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats. However, little is known about the biomarkers and mechanisms underlying Pb, Cd, and Hg mixture-induced neurological impairments. A combined analysis of metabolomic and proteomic data may reveal heavy metal-induced alterations in metabolic and protein profiles, thereby improving our understanding of the molecular mechanisms underlying heavy metal-induced neurological impairments. Therefore, brain tissue and serum samples were collected from rats exposed to a Pb, Cd, and Hg mixture for proteomic and metabolomic analyses, respectively. The analysis revealed 363 differential proteins in the brain and 206 metabolites in serum uniquely altered in the Pb, Cd, and Hg mixture exposure group, compared to those of the control group. The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism, phenylalanine metabolism, and tryptophan metabolism. We further identified that the levels of arachidonic acid (C20:4 n-3) and, adrenic acid (C22:4 n-3) were elevated and that kynurenic acid (KA) and quinolinic acid (QA) levels and the KA/QA ratio, were decreased in the group exposed to the Pb, Cd, and Hg mixture. A joint analysis of the proteome and metabolome showed that significantly altered proteins such as LPCAT3, SLC7A11, ASCL4, and KYAT1 may participate in the neurological impairments induced by the heavy metal mixture. Overall, we hypothesize that the dysregulation of ferroptosis and kynurenine pathways is associated with neurological damage due to chronic exposure to a heavy metal mixture.

Cadmium exposure induces histological damage and cytotoxicity in the cardiovascular system of mice.

Epidemiological studies have reported an association between chronic cadmium (Cd) exposure and increased cardiovascular risk; however, their causal relationship remains unclear. The aim of this study is to explore the effects of Cd exposure on the cardiac and arterial systems in mice. According to the concentration of cadmium chloride in drinking water, male mice were randomly divided into control and low-dose and high-dose Cd exposure groups. The intervention duration was 12 weeks. In cardiac tissues, Cd exposure led to focal necrosis, myofibril disarray, perivascular and interstitial fibrosis, and disorganized sarcomere structures. Cd also induced the apoptosis of cardiomyocytes and increased the expression levels of matrix metalloproteinase (MMP)-2 and MMP-14 in cardiac tissues. In the arterial tissues, Cd exposure damaged the intimal and medial layers of the aorta. Cd further reduced the viability of aortic smooth muscle cells in vitro. This study provides evidence for the Cd-induced damage of the cardiovascular system, which may contribute to various cardiovascular diseases.

The presence of microplastics (MPs) reduces the toxicity of cadmium (Cd) to Cirrhinus mrigala larva

Cumulative studies have shown that microplastics (MPs) and cadmium (Cd) co-exist widely, but their combined toxic effects on aquatic organisms are still not well understood. In this study, Cirrhinus mrigala larvae were exposed to single and binary combinations for 7 days, and the growth performance, survival, intestinal contaminant migration, intestinal histopathology, enzyme activity, and expression of antioxidant-related and detoxification-related genes were measured. The results showed that PS-MPs, Cd, and their combined exposure cause intestinal tissue damage, which in turn affects the growth and survival of C. mrigala larvae, and combined exposure of PS-MPs and Cd reduces stagnant growth and death caused by single Cd exposure. Under both single and binary exposure, PS-MPs can accumulate in the intestine of C. mrigala larvae, but Cd-induced damage to intestinal tissues can increase the accumulation of PS-MPs in the intestine of C. mrigala larvae. PS-MPs, Cd and their combined exposure can cause abnormalities in enzyme activity and expression of antioxidant genes and detoxification genes. The results of continuous 7-day dynamic monitoring showed that the relative expression of cat in the Cd exposure group was significantly higher than that of the control group on days 1, 2 and 4; the relative expression of gpx was significantly higher than that of the control group on days 3, 4 and 7; the relative expression of mnsod was significantly higher than that of the control group on days 1, 3 and 7; and the relative expression of cusod was significantly higher than that of the control group on days 4, 6 and 7. These results indicated that the presence of MPs acted as an antagonist, reducing the toxicity of Cd to aquatic organisms. Overall, this study contributes to further understanding of the inter-regulatory relationship between MPs and Cd and the combined toxic effects on aquatic organisms.

Physiological and biochemical responses of the estuarine pulmonate mud snail, Amphibola crenata, sub-chronically exposed to waterborne cadmium

Physiological and biochemical responses of the pulmonate mud snail, Amphibola crenata, to waterborne cadmium (Cd) were investigated to determine the mechanisms of toxicity and impacts of a 21-d Cd exposure. Mud snails were exposed to nominal Cd concentrations of 0, 0.2, 4 and 8 mg L − 1 and bioaccumulation, whole animal physiological (oxygen consumption, ammonia excretion and oxygen:nitrogen), and tissue level biochemical (catalase activity, lipid peroxidation, glycogen, glucose and protein) endpoints were measured every 7 days. At the two highest Cd exposure concentrations complete mortality was observed over 21-d. In surviving animals, oxygen consumption declined and ammonia excretion rate increased with Cd exposure concentration and duration. The increased ammonia excretion likely reflected enhanced protein metabolism as suggested by a reduced oxygen:nitrogen (O:N). Increasing waterborne Cd concentration and exposure time led to increasing metal accumulation in all tissues. The snail viscera showed the highest Cd accumulation. Both catalase activity and lipid peroxidation in the viscera significantly increased with Cd exposure concentration and time, whereas, the foot muscle and remaining tissues (kidney, mantle, remaining digestive tissues and heart) showed increased catalase activity and lipid peroxidation at higher Cd concentrations (4 and 8 mg L − 1), suggestive of an effect of Cd on oxidative stress. Over the course of 21 days, Cd exposure resulted in significantly lower levels of glycogen in viscera relative to Cd-free controls, reflecting an increased energy demand. Haemolymph glucose rose initially and then fell with increased exposure duration, while haemolymph protein generally exhibited an increased concentration in Cd-exposure groups, reflecting the changes in energy substrates noted for somatic tissues. These results suggest that the physiological and biochemical responses of A. crenata to Cd are conserved relative to other aquatic animals, and were tissue-specific, dose- and time-dependant.

JAK2/STAT3 Signaling Pathway and Klotho Gene in Cadmium-induced Neurotoxicity In Vitro and In Vivo.

Cadmium (Cd), a common heavy metal in the environment, is associated with cognitive impairment. In the present study, we carried out a preliminary inquiry to explore whether Cd causes neurotoxicity by regulating the JAK2/STAT3 signaling pathway and affecting the expression of klotho genes in vivo and in vitro, providing clues for the mechanism of Cd-induced cognitive dysfunction. The rat samples were injected with Cd chloride solution for 14weeks, and the memory function of the rats was detected. Different concentrations of Cd and JAK2/STAT3 signaling pathway inhibitors were used to treat PC12 cells and thus detect the apoptosis rate. The protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, and klotho in rat and PC12 cell were detected by ELISA and Western blot, respectively. With the increase in exposure dose, the memory function of rats was severely impaired. The expression of p-JAK2 and p-STAT3 proteins was significantly up-regulated, whereas that of klotho was significantly down-regulated both in vivo and in vitro (p < 0.05). In comparison with the high-dose Cd exposure group, after adding tyrphostin AG490 (AG490), the apoptosis rate of PC12 cells increased, whereas the phosphorylation levels of JAK2 and STAT3 in the cells decreased significantly (p < 0.05). Cd exposure may cause neurotoxicity by regulating the JAK2/STAT3 signaling pathway and down-regulating klotho protein expression, leading to cognitive dysfunction.

Effects of subacute cadmium exposure and subsequent deferiprone treatment on cadmium accumulation and on the homeostasis of essential elements in the mouse brain

IntroductionCadmium (Cd) is а hazardous multi-organ toxin. In this study, we provide the first results about the effect of oral administration of deferiprone (DFP) on Cd accumulation and on the homeostasis of essential elements in the brain of Cd-exposed mice. MethodsAdult Institute of Cancer Research (ICR) male mice were randomized into four experimental groups: untreated controls – administered distilled water for 28 days; Cd-exposed group – exposed to 18 mg/kg body weight (b.w.) Cd(II) acetate for 14 days followed by the administration of distilled water for two weeks; Cd + DFP (low dose) – Cd-intoxicated mice subsequently treated with 19 mg/kg b.w. DFP for two weeks; and Cd + DFP (high dose) – Cd-exposed mice administered high-dose DFP (135 mg/kg b.w.) for 14 days. Brains were subjected to inductively coupled plasma-mass spectrometry (ICP-MS) and histological analysis. ResultsThe results revealed that exposure of mice to Cd for 14 days significantly increased Cd concentration and significantly decreased magnesium (Mg), phosphorus (P), and zinc (Zn) contents in the brain compared to untreated controls. This effect was accompanied by necrotic-degenerative changes in both the cerebrum and cerebellum. Oral administration of low-dose DFP to Cd-exposed mice decreased the concentration of the toxic metal in the brain by 16.37% and restored the concentration of the essential elements to normal control values. Histological analysis revealed substantially improved cerebral and cerebellar histoarchitectures. In contrast, oral administration of high-dose DFP increased Cd content and significantly decreased selenium (Se) concentration in the brain. Necrotic neurons and Purkinje cells were still observed in the cerebral and cerebellar cortices. ConclusionThe results demonstrated that oral administration of DFP at low doses has a better therapeutic potential for the treatment of Cd-induced brain damage compared to high doses.

Subacute Cadmium Exposure Induces Necroptosis in Swine Lung via Influencing Th1/Th2 Balance.

Cadmium (Cd) is a type of toxic substance, which widely exists in nature. However, the effect of Cd exposure on the toxicity of swine lungs and its underlying mechanism involved have not yet been reported. In our study, we divided swine into two groups, including a control group (C group) and Cd-exposed group. Swine in the C group were fed a basic diet, whereas swine in the Cd group were fed a 20mg Cd/kg diet. Immunofluorescence, qRT-PCR, western blot analysis, and H&E staining were performed to detect necroptosis-related indicators. Our results found that after Cd exposure, Th1/Th2 imbalance occurred, miR-181-5p was down-regulated, TNF-α expression was increased, and the NF-κB/NLRP3 and JAK/STAT pathways and RIPK1/RIPK3/MLKL axis were activated. Furthermore, histopathological examination showed necrosis in swine lung after Cd exposure. Together, the above-mentioned results indicate that subacute Cd exposure is closely linked with necroptosis in swine lung. Our study provided evidence that Cd may act through miR-181-5p/TNF-α to induce necroptosis in swine lung. The findings of this study supplement the toxicological study of Cd and provide a reference for comparative medicine.

Cadmium exposure decreases fasting blood glucose levels and exacerbates type-2 diabetes in a mouse model.

Although the effects of cadmium (Cd) on the development of diabetes have been extensively investigated, the relationship between Cd exposure and the severity of established diabetes is unclear. Herein, we investigate the effects of long-term exposure to Cd in a streptozotocin-induced mouse model of type-2 diabetes mellitus (T2DM) and the underlying mechanism. C57BL/6 Mice were divided into the following four groups: (1) control group; (2) Cd-exposed group; (3) diabetic group; (4) Cd-exposed diabetic group. Cd exposure was established by the administration of 155 ppm CdCl2 in drinking water. After 25 weeks of treatment, serum fasting glucose and insulin were measured. Meanwhile, the liver and pancreas specimens were sectioned and stained with Hematoxylin and eosin. Gluconeogenesis, glycolysis, lactate concentration, and fibrosis in liver were evaluated. Clinical signs attributable to diabetes were more apparent in Cd-exposed diabetic mice, while no effects of Cd exposure were found on non-diabetic mice. Cd exposure significantly decreased fasting blood glucose (FBG) levels in diabetic group. We further demonstrated that the glycolysis related hepatic enzymes, pyruvate kinase M2 (PKM-2) and lactic dehydrogenase A (LDHA) were both increased, while the gluconeogenesis related hepatic enzymes, phosphoenolpyruvate-1 (PCK-1) and glucose-6-phosphatase (G6Pase) were both decreased in Cd exposed diabetic mice, indicating that Cd increased glycolysis and inhibited gluconeogenesis in diabetic model. Moreover, lactate accumulation was noted accompanied by the increased inflammation and fibrosis in the livers of diabetic mice following Cd exposure. Cd exposure disturbed glucose metabolism and exacerbated diabetes, providing a biological relevance that DM patients are at greater risk when exposed to Cd.

AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver

The experiment was conducted to investigate the effects of Cadmium (Cd) on growth performance, blood biochemical parameters, oxidative stress, hepatocyte apoptosis and autophagy of weaned piglets. A total of 12 healthy weaned piglets were randomly assigned to the control and the Cd group, which were fed with a basal diet and the basal diet supplemented with 15 ± 0.242 mg/kg CdCl2 for 30 d, respectively. Our results demonstrated that Cd significantly decreased final body weight, average daily feed intake (ADFI), average daily gain (ADG) and increased feed-to-gain (F/G) ratio (P < 0.05). For blood biochemical parameters, Cd treatment significantly decreased the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), total protein, albumin, copper content and iron content (P < 0.05). In addition, liver injury was observed in the Cd-exposed group. Our results also demonstrated that Cd exposure contributed to the production of ROS, activated the AMPK/PPAR-γ/NF-κB pathway (increasing the expressions of P-AMPK/AMPK, NF-κB, I-κB-β, COX-2, and iNOS, decreasing the expressions of PPAR-γ and I-κB-α), finally induced autophagy (increasing the expressions of Beclin-1, the ratio of LC3-II/LC3-I and p62), and apoptosis (increasing the expressions of Bax, Bak, Caspase-9, and Caspase-3, decreasing the expression of Bcl-2). Overall, these findings revealed the vital role of AMPK/PPAR-γ/NF-κB pathway in Cd-induced liver apoptosis and autophagy, which provided deeper insights into a better understanding of Cd-induced hepatotoxicity.

Common mechanisms cannot explain time- and dose-dependent DNA methylation changes in earthworms exposed to cadmium

DNA hypermethylation caused by environmental pollutants like cadmium (Cd) has already been demonstrated in many invertebrates, including earthworms. However, the exact epigenetic mechanisms that drive this hypermethylation are largely unknown and even basic DNA methylation and demethylation processes are hardly characterized. Therefore, we used an important bioindicator, the earthworm Lumbricus terrestris, as a model organism to determine time- and dose-dependent effects of Cd on global and gene-specific DNA methylation and its underlying mechanisms. We revealed Cd-induced adenine and cytosine hypermethylation using specific antibodies in dot blots and found that the methylation level of adenine compared to cytosine changed even to a bigger extent. However, the levels of hydroxymethylated cytosine did not differ between treatment groups. General methylation and demethylation components like methyltransferases (DNMT1 and 3), and ten-eleven translocation (TET) genes were confirmed in L. terrestris by quantitative RealTime PCR. However, neither gene expression, nor DNMT and TET enzyme activity showed significant differences in the Cd exposure groups. Using bisulfite conversion and sequencing, gene body methylation (gbm) of metallothionein 2 (MT2), one of the most important detoxification proteins, was characterized. Cd-dependent changes in MT2 gbm could, however, not be correlated to MT2 gene activity evaluated by quantitative RealTime PCR.Future directions as well as missing links are discussed in the present study hinting towards the importance of studying epigenetic marks and mechanistic insights in a broad variety of species to deepen our knowledge on the effects of changing environmental conditions.

Cadmium exposure promotes activation of cerebrum and cerebellum ferroptosis and necrosis in swine

Cadmium(Cd) is a toxic and carcinogenic heavy metal pollutant leading to serious damage in various organs. Ferroptosis and necrosis as inflammation-related cell death are involved in several diseases of nervous system. In the present study, 10 weaning piglets with similar weight for 6 weeks were randomly divided into two groups. The daily grain containing 0 mg and 20 mg/kg of Cd chloride was fed in 20–26 ℃ environment, animals were sacrificed to collect cerebrum and cerebellum tissues after 40 days. Morphology and ultrastructure results were observed using HE and TEM. Moreover, molecular biological technologies western blot and qRT-PCR were used to detect the expression abundance of genes. Cerebrum and cerebellum injury was observed in Cd-exposed group, antioxidant capacity decreased significantly and oxidative stress increased; immunofluorescence, real-time quantification, and western blot results showed decreased necrosis genes and increased ferroptosis pathway genes abundance in cerebrum, whereas the results were reversed in cerebellum. These results indicated that Cd exposure can activated necrosis and ferroptosis pathways by increased oxidative stress, further resulting in cerebrum and cerebellum damage in pigs. These findings may provide a theoretical basis for early monitoring of Cd exposure in environment.